Despite the remarkable improvement in outcome for patients with acute promyelocytic leukemia (APL) since the incorporation of all trans-retinoic acid (ATRA), as many as 30% of patients are not cured with primary therapy. Secondary leukemias and myelodysplastic syndromes are increasingly reported following treatment according to current protocols that include three or more cycles of consolidation chemotherapy. Thus, minimizing exposure to excessive cytotoxic agents while maintaining or increasing the cure rate must represent priority goals for future developmental APL therapy. Arsenic trioxide (ATO) has demonstrated extraordinary single-agent activity against relapsed APL, inducing complete remissions in 70 - 90% of patients. The research proposed in this application investigates the incorporation of ATO into the primary curative therapy of newly diagnosed APL. A Phase II multicenter clinical trial will be performed in which ATO is substituted for etoposide during a single intensive consolidation cycle. This trial is based on a prior trial in which a single intensive consolidation appeared to yield comparable remissions to more conventional regimens which include two to three cycles of consolidation therapy, potentially minimizing short- and long-term toxicity, including secondary malignancies. The overall hypothesis is that substitution of ATO for the less active etoposide in a single cycle of consolidation chemotherapy will lead to equivalent durable remissions and cures, with less short- and long-term toxicity. To enable assessment of the success of this pilot approach in a rapid time frame, the primary endpoint of this study will be the determination of the frequency of maintenance of remissions at one year in which PML-RARalpha transcript remains undetectable above 10 E-4, the threshold which predicts relapse. This trial will utilize a novel quantitative rt-PCR technique to monitor samples of peripheral blood for adequacy of ongoing remission and evidence of early relapse. This assay will greatly ease the burden of disease monitoring for patients, who currently undergo bone marrow aspirations every three - six months. This assay will also enable determination of the log-reduction of tumor contamination attributable to this novel consolidation approach. Success of this trial will potentially be followed by the testing of regimen against more conventional and more extensive treatment for APL in a Phase III trial. [unreadable] [unreadable] [unreadable]